Dimethylformamide → Methyl 4-cyano-2-fluorobenzoate

HRID 1673146Notes

Reaction equation

HRID 1673146 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1.[CH3:13][N:14](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[C:13]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([F:12])[CH:3]=1)#[N:14]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 113453114-Bromo-2-fluoro-benzoic acid methyl ester

Product 1

HCID 15278726Methyl 4-cyano-2-fluorobenzoateYield 80%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A solution of methyl 4-bromo-2-fluorobenzoate (10.0 g, 43 mmol), zinc cyanide (10.0 g, 86 mmol) and palladium tetrakis(triphenylphosphine) (2.5 g, 0.64 mmol) in N,N-dimethylformamide (100 mL) was stirred at 80° C. overnight. After cooling, the mixture was partitioned between ethyl acetate and brine and the organic phase washed with water and concentrated. The residue was purified by flash chromatography on silica gel (1:5 ethyl acetate/hexane) to afford 6.1 g (80%) of the title compound. MS (DCI): m/z 180 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between ethyl acetate and brine
  3. washthe organic phase washed with water
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on silica gel (1:5 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3fa1746c03924152bc039014cecdfa8a
Source dataset
uspto-grants-2011_08
Patent number
US07999117B2

Reaction notes

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